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Expression of retinoid‐responsive genes occurs in colorectal carcinoma‐derived cells irrespective of the presence of resistance to all‐trans retinoic acid
Author(s) -
Waliszewski Przemyslaw,
Waliszewska Miroslawa K.,
Gupta Manjuela,
Milsom Jeffrey W.,
Hurst Robert E.
Publication year - 1997
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/(sici)1096-9098(199711)66:3<156::aid-jso2>3.0.co;2-b
Subject(s) - retinoid , retinoic acid , retinoid x receptor alpha , retinoid x receptor gamma , retinoid x receptor beta , retinoic acid receptor alpha , retinoic acid receptor , retinoid x receptor , retinoic acid receptor beta , cancer research , biology , microbiology and biotechnology , signal transduction , receptor , nuclear receptor , cell culture , endocrinology , medicine , gene , biochemistry , transcription factor , genetics
Background and Objectives Retinoids are metabolized in human intestinal epithelial cells to all‐trans retinoic acid; however, it is unknown whether these cells express retinoid receptors, and whether sensitivity or resistance to the hormone is associated with a particular pattern of expression of retinoid‐responsive genes. Methods Northern blot analysis and reverse transcriptase polymerase chain reaction (RT‐PCR) were used to identify mRNAs for retinoid receptors. Both Relative RT‐PCR and transfection of retinoid‐inducible plasmid were applied to test functionality of the pathway in a model system for colorectal carcinoma progression (primary SW480, all‐trans retinoic acid‐sensitive cells vs. metastatic SW620, ‐insensitive cells). Results Three colorectal carcinoma‐derived cell lines were inhibited by the hormone. Retinoic acid receptor type α (hRARα) and retinoid X receptor type α (hRXRα) mRNAs were detected in normal enterocytes, colonocytes, and in all colorectal carcinoma‐derived cells studied. Primary carcinomas and metastatic lesions expressed high amounts of hRARα receptor protein, showing no simple correlation between the amounts of mRNA and receptor protein. No pattern of expression of the retinoid‐responsive genes was associated with sensitivity or resistance to the retinoid. Expression of the genes occurred irrespective of resistance to the hormone or inactivity of the pathway. Conclusions Colonocytes possess a molecular system for transduction of the retinoid signal. All‐trans retinoic acid modifies gene expression and inhibits proliferation of these cells. Therefore, retinoids are likely to be effective in chemoprevention of colorectal carcinoma. J. Surg. Oncol. 1997;66:156–167. © 1997 Wiley‐Liss, Inc.